Within an Antarctic Sea Squirt, Scientists Discover a Bacterial Species With Promising Anti-Melanoma Properties

Within an Antarctic Sea Squirt, Scientists Discover a Bacterial Species With Promising Anti-Melanoma Properties

Within an Antarctic Sea Squirt, Scientists Discover a Bacterial Species With Promising Anti-Melanoma Properties

December 1, 2021
RENO, NEV.

By Kelsey Fitzgerald

Antarctic Sea Squirt
Melanoma
Health

Above: Late spring at Arthur Harbor. The waters surrounding Anvers Island, Antarctica, are home to a species of sea squirt called Synoicum adareanum. New research has traced the production of palmerolide A, a key compound with anti-melanoma properties, to a member of this sea squirt’s microbiome.

Credit: Alison E. Murray, DRI

New study brings important advances for Antarctic science and natural products chemistry

There are few places farther from your medicine cabinet than the tissues of an ascidian, or “sea squirt,” on the icy Antarctic sea floor – but this is precisely where scientists are looking to find a new treatment for melanoma, one of the most dangerous types of skin cancer.

In a new paper that was published today in mSphere, a research team from DRI, Los Alamos National Laboratory (LANL), and the University of South Florida (USF) made strides toward their goal, successfully tracing a naturally-produced melanoma-fighting compound called “palmerolide A” to its source: a microbe that resides within Synoicum adareanum, a species of ascidian common to the waters of Antarctica’s Anvers Island archipelago.

“We have long suspected that palmerolide A was produced by one of the many types of bacteria that live within this ascidian host species, S. adareanum,” explained lead author Alison Murray, Ph.D., research professor of biology at DRI. “Now, we have actually been able to identify the specific microbe that produces this compound, which is a huge step forward toward developing a naturally-derived treatment for melanoma.”

Synoicum adareanum

Synoicum adareanum in 80 feet of water at Bonaparte Point, Antarctica. New research has traced the production of palmerolide A, a key compound with anti-melanoma properties, to a suite of genes coded in the genome by a member of this sea squirt’s microbiome.

Credit: Bill J. Baker, University of South Florida.
Discovery of an Antarctic ascidian-associated uncultivated Verrucomicrobia with antimelanoma palmerolide biosynthetic potential

The full study, Discovery of an Antarctic ascidian-associated uncultivated Verrucomicrobia with anti-melanoma palmerolide biosynthetic potential, is available from mSphere: https://doi.org/10.1128/msphere.00759-21.

The bacterium that the team identified is a member of a new and previously unstudied genus, Candidatus Synoicihabitans palmerolidicus. This advance in knowledge builds on what Murray and her colleagues have learned across more than a decade of research on palmerolide A and its association with the microbiome (collective suite of microbes and their genomes) of the host ascidian, S. adareanum.

In 2008, Murray worked with Bill Baker, Ph.D., professor of chemistry at USF and Christian Riesenfeld, Ph.D., postdoctoral researcher at DRI to publish a study on the microbial diversity of a single S. adareanum organism. In 2020, the team expanded to include additional researchers from LANL, USF, and the Université de Nantes, and published new work identifying the “core microbiome” of S. adareanum – a common suite of 21 bacterial species that were present across 63 different samples of S. adareanum collected from around the Anvers Island archipelago.

In the team’s latest research, they looked more closely at the core microbiome members identified in their 2020 paper to determine which of the 21 types of bacteria were responsible for the production of palmerolide A. They conducted several rounds of environmental genome sequencing, followed by automated and manual assembly, gene mining, and phylogenomic analyses, which resulted in the identification of the biosynthetic gene cluster and palmerolide A-producing organism.

“This is the first time that we’ve matched an Antarctic natural product to the genetic machinery that is responsible for its biosynthesis,” Murray said. “As an anti-cancer therapeutic, we can’t just go to Antarctica and harvest these sea squirts en masse, but now that we understand the underlying genetic machinery, it opens the door for us to find a biotechnological solution to produce this compound.”

“Knowing the producer of palmerolide A enables cultivation, which will finally provide sufficient quantity of the compound for needed studies of its pharmacological properties,” added Baker.

 

A diver collects samples of Synoicum adareanum in support of a microbiome and biosynthetic gene cluster study. Palmer Station Antarctica, March 2011.

Credit: Bill Dent, University of South Florida.

Many additional questions remain, such as how S. adareanum and its palmerolide-producing symbiont are distributed across the landscape in Antarctic Oceans, or what role palmerolide A plays in the ecology of this species of ascidian.  Likewise, a detailed investigation into how the genes code for the enzymes that make palmerolide A is the subject of a new report soon to be published.

To survive in the harsh and unusual environment of the Antarctic sea floor, ascidians and other invertebrates such as sponges and corals have developed symbiotic relationships with diverse microbes that play a role in the production of features such as photoprotective pigments, bioluminescence, and chemical defense agents. The compounds produced by these microbes may have medicinal and biotechnological applications useful to humans in science, health and industry. Palmerolide A is one of many examples yet to be discovered.

“Throughout the course of disentangling the many genomic fragments of the various species in the microbiome, we discovered that this novel microbe’s genome appears to harbor multiple copies of the genes responsible for palmerolide production,” said Patrick Chain, Ph.D., senior scientist and Laboratory Fellow with LANL. “However the role of each copy, and regulation, for example, are unknown. This suggests palmerolide is likely quite important to the bacterium or the host, though we have yet to understand it’s biological or ecological role within this Antarctic setting.”

“This is a beautiful example of how nature is the best chemist out there,” Murray added. “The fact that microbes can make these bioactive and sometimes toxic compounds that can help the hosts to facilitate their survival is exemplary of the evolutionary intricacies found between hosts and their microbial partners and the chemical handshakes that are going on under our feet on all corners of the planet.”

Diver in the Antarctic Peninsula

Andrew Schilling (University of South Florida) dives in 100 feet of water at Cormorant Wall, Antarctica. Samples for microbiome characterization were collected by SCUBA divers working in the chilly subzero seas off Anvers Island, in the Antarctic Peninsula.

Credit: Bill J. Baker, University of South Florida. 

More information:

The full study, Discovery of an Antarctic ascidian-associated uncultivated Verrucomicrobia with antimelanoma palmerolide biosynthetic potential, is available from mSphere: https://doi.org/10.1128/msphere.00759-21.

Study authors included Alison Murray (DRI), Chein-Chi Lo (LANL), Hajnalka E. Daligault (LANL), Nicole E. Avalon (USF), Robert W. Read (DRI), Karen W. Davenport (LANL), Mary L. Higham (DRI), Yuliya Kunde (LANL), Armand E.K. Dichosa (LANL), Bill J. Baker (USF), and Patrick S.G. Chain (LANL).

This study was made possible with funding from the National Institutes of Health (CA205932), the National Science Foundation (OPP-0442857, ANT-0838776, and PLR-1341339), and DRI (Institute Project Assignment).

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About DRI

The Desert Research Institute (DRI) is a recognized world leader in basic and applied environmental research. Committed to scientific excellence and integrity, DRI faculty, students who work alongside them, and staff have developed scientific knowledge and innovative technologies in research projects around the globe. Since 1959, DRI’s research has advanced scientific knowledge on topics ranging from humans’ impact on the environment to the environment’s impact on humans. DRI’s impactful science and inspiring solutions support Nevada’s diverse economy, provide science-based educational opportunities, and inform policymakers, business leaders, and community members. With campuses in Las Vegas and Reno, DRI serves as the non-profit research arm of the Nevada System of Higher Education. For more information, please visit www.dri.edu. 

About The University of South Florida

The University of South Florida is a high-impact global research university dedicated to student success. Over the past 10 years, no other public university in the country has risen faster in U.S. News and World Report’s national university rankings than USF. Serving more than 50,000 students on campuses in Tampa, St. Petersburg and Sarasota-Manatee, USF is designated as a Preeminent State Research University by the Florida Board of Governors, placing it in the most elite category among the state’s 12 public universities. USF has earned widespread national recognition for its success graduating under-represented minority and limited-income students at rates equal to or higher than white and higher income students. USF is a member of the American Athletic Conference. Learn more at www.usf.edu.

About Los Alamos National Laboratory

Los Alamos National Laboratory, a multidisciplinary research institution engaged in strategic science on behalf of national security, is managed by Triad, a public service oriented, national security science organization equally owned by its three founding members: Battelle Memorial Institute (Battelle), the Texas A&M University System (TAMUS), and the Regents of the University of California (UC) for the Department of Energy’s National Nuclear Security Administration. Los Alamos enhances national security by ensuring the safety and reliability of the U.S. nuclear stockpile, developing technologies to reduce threats from weapons of mass destruction, and solving problems related to energy, environment, infrastructure, health, and global security concerns.

 

New study reveals key information about the microbiome of an important anticancer compound-producing Antarctic marine invertebrate

New study reveals key information about the microbiome of an important anticancer compound-producing Antarctic marine invertebrate

New study reveals key information about the microbiome of an important anticancer compound-producing Antarctic marine invertebrate

RENO, NEV.
JUNE 25, 2020

Microbiology
Melanoma
Ascidians

Could the cure for melanoma – the most dangerous type of skin cancer – be a compound derived from a marine invertebrate that lives at the bottom of the ocean? A group of scientists led by Alison Murray, Ph.D. of the Desert Research Institute (DRI) in Reno think so, and are looking to the microbiome of an Antarctic ascidian called Synoicum adareanum to better understand the possibilities for development of a melanoma-specific drug.

 Ascidians, or “sea squirts”, are primitive, sac-like marine animals that live attached to ocean-bottoms around the world, and feed on plankton by filtering seawater. S. adareanum, which grows in small colonies in the waters surrounding Antarctica, is known to contain a bioactive compound called “Palmerolide A” with promising anti-melanoma properties – and researchers believe that the compound is produced by bacteria that are naturally associated with S. adareanum.

In a new paper published this month in the journal Marine Drugs, Murray and collaborators from the University of South Florida, the Los Alamos National Laboratory, and the Université de Nantes, France, present important new findings measuring palmerolide levels across samples collected from Antarctica’s Anvers Island Archipelago and characterizing the community of bacteria that make up the microbiome of S. adareanum

“Our longer-term goal is to figure out which of the many bacteria within this species is producing palmerolide, but to do this, there is a lot we need to learn about the microbiome of S. adareanum,” Murray said. “Our new study describes many advances that we have made toward that goal over the last few years.”

Synoicum adareanum

Synoicum adareanum: The Antarctic sea squirt, Synoicum adareanum at 80’ (24 meters) lives amongst the red algae, bryozoans and starfish on the seafloor. It is a non-motile benthic species that gets its nutrition from microorganisms and organic carbon in the seawater. Its microbiome hosts a suite of different microorganisms that can provide defenses against predation and infection in some cases. Tissues of this animal were found to contain high levels of a compound that is active against melanoma, which is thought to be produced by a member of the sea squirt’s microbiome.

Credit: Bill Baker, USF

In 2008, Murray worked with Bill Baker, Ph.D., of the University of South Florida, and DRI postdoctoral researcher Christian Riesenfeld, Ph.D., to publish a study on the microbial diversity of one individual S. adareanum. Their new study builds upon this research by characterizing the microbial diversity of 63 different individuals that were collected from around Anvers Island.

Their results identify a what the researchers call the “core microbiome” of the species – a common suite of 21 bacterial taxa that were present in more than 80 percent of samples, and six bacterial taxa that were present in all 63 samples.

“It is a key “first” for Antarctic science to have been able to find and identify this core microbiome in a fairly large regional study of these organisms,” Murray said. “This is information that we need to get to the next step of identifying the producer of palmerolide.”

Another “first” for Antarctic science, and for the study of natural products in nature in general, was a comparison of palmerolide levels across all 63 samples that showed the compound was present in every specimen at high (milligram per gram specimen tissue) levels, but the researchers found no trends between sites, samples, or microbiome bacteria. Additional analysis looking at the co-occurrence relationships of the taxa across the large data set showed some of the ways that bacteria are interacting with each other and with the host species in this marine ecosystem.

 “The microbiome itself is unique in composition from other ascidians, and seems to be pretty interesting, with a lot of interaction,” Murray said. “Our study has opened the doors to understand the ecology of this system.”

From the assemblage of bacteria that the researchers have identified as making up the core microbiome of S. adareanum, they next hope to use a genomics approach to finally be able to identify which of the bacteria are producing palmerolide – an important and needed advancement toward the development of a melanoma treatment.  

“It would be a really big deal to use this compound to develop a drug for fighting melanoma, because there are just so few drugs at the moment that can be used to treat it,” Murray said. “If we can identify the bacteria that produce this chemical, and with its genome understand how to cultivate it in a laboratory setting, this would enable us to provide a sustainable supply of palmerolide that would not rely on harvesting wild populations of this species in Antarctica.”

 

Anvers Island Antarctica

Anvers Island Antarctica: Samples for microbiome characterization were collected by SCUBA divers working on the sea ice off Anvers Island, in the Antarctic Peninsula. Diving through holes cut in the sea ice requires dry suites, and relatively short dive times. (photographed Prof. Bill Baker in the hole, and his graduate student Chris Petri suited on the sled).

Credit: Maggy Amsler

DNA-stained micrograph

DNA-stained micrograph: Cultivation efforts led to isolation of a new bacterial species affiliated with the Pseudovibrio genus – a group known to produce bioactive compounds – this is the first cold-adapted member of this genus. This strain has unusual branching morphology (seen in the DNA-stained micrograph), and storage granules that appear yellow.

Credit: Eric Lundin, DRI

“It is a key “first” for Antarctic science to have been able to find and identify this core microbiome in a fairly large regional study of these organisms,” Murray said. “This is information that we need to get to the next step of identifying the producer of palmerolide.”

Additional information

The full text of the study, “Uncovering the Core Microbiome and Distribution of Palmerolide in Synoicum adareanum Across the Anvers Island Archipelago, Antarctica,” is available from Marine Drugs: https://www.mdpi.com/1660-3397/18/6/298/htm

This research was supported by the National Institute of Health, National Cancer Institute, and the National Science Foundation.

 

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About the Desert Research Institute

The Desert Research Institute (DRI) is a recognized world leader in basic and applied interdisciplinary research. Committed to scientific excellence and integrity, DRI faculty, students, and staff have developed scientific knowledge and innovative technologies in research projects around the globe. Since 1959, DRI’s research has advanced scientific knowledge, supported Nevada’s diversifying economy, provided science-based educational opportunities, and informed policy makers, business leaders, and community members. With campuses in Reno and Las Vegas, DRI serves as the non-profit research arm of the Nevada System of Higher Education. For more information, please visit www.dri.edu.

 

Media Contact

Justin Broglio
Communications Manager, Desert Research Institute
775-762-8320
Justin.Broglio@dri.edu
@DRIScience

International Consortium of Scientists Propose New Naming System for Uncultivated Bacteria and Archaea

International Consortium of Scientists Propose New Naming System for Uncultivated Bacteria and Archaea

International Consortium of Scientists Propose New Naming System for Uncultivated Bacteria and Archaea

RENO, NEV.
JUNE 8, 2020

Microbiology
Nomenclature
Taxonomy

The long-standing rules for assigning scientific names to bacteria and archaea are overdue for an update, according to a new consensus statement backed by 119 microbiologists from around the globe.

Bacteria and archaea (single-celled organisms that lack cell nuclei) make up two of the three domains of life on Earth, and are named according to the International Code of Nomenclature of Prokaryotes (ICNP; the Code). At present, the Code only recognizes species that can be grown from cultures in laboratories – a requirement that has long been problematic for microbiologists who study bacteria and archaea in the wild.

Since the 1980s, microbiologists have used genetic sequencing techniques to sample and study DNA of microorganisms directly from the environment, across diverse habitats ranging from Earth’s icy oceans to deep underground mines to the surface of human skin. For a vast majority of these species, no method yet exists for cultivating them in a laboratory, and thus, according to the Code, they cannot be officially named.

“There has been a surge in recent years in genome-based discoveries for archaea and bacteria collected from the environment, but no system in place to formally name them, which is creating a lot of chaos and confusion in the field,” said Alison Murray, Ph.D., Research Professor of Biology at the Desert Research Institute (DRI) in Reno. “Being able to represent the diversity of uncultivated organisms known by their genome sequences in a common language is incredibly important.”

deep sea vent

Deep-sea hydrothermal vent chimney from the Mid-Atlantic Ridge. Many new microbial genomes have been described from these environments. 

Credit: Anna-Louise Reysenbach and Woods Hole Oceanographic Institution.

In an article published this week in the journal Nature Microbiology, Murray and her collaborators present the rationale for updating the existing regulations for naming new species of bacteria and archaea, and propose two possible paths forward.

As a first option, the group proposes formally revising the Code to include uncultivated bacteria and archaea represented by DNA sequence information, in place of the live culture samples that are currently required. As an alternative, they propose creating an entirely separate naming system for uncultivated organisms that could be merged with the Code at some point in the future. 

“For researchers in this field, the benefits of moving forward with either of these options will be huge,” said Brian Hedlund, Ph.D., Professor of Life Sciences at the University of Nevada, Las Vegas. “We will be able to create a unified list of all of the uncultivated species that have been discovered over the last few decades and implement universal quality standards for how and when a new species should be named.”

For example, researchers who use DNA sequencing to study the human microbiome – the thousands of species of Bacteria and Archaea that that live inside and on the human body – would have a means of assigning formal names to the species they identify that are not yet represented in culture collections. This would improve the ability for researchers around the world to conduct collaborative studies on topics such as connections between diet and gut bacteria in different human populations, or to build off of previous research.

Antarctic seawater microbes

This micrograph is a representative Antarctic marine sample of bacteria and archaea that has been stained with a fluorescent dye (DAPI) that binds to DNA.  A typical sample of Antarctic seawater harbors 200 to over 600 different taxa based on the diversity of 16S rRNA gene sequences. Only a small fraction of this diversity, < 1%, has been cultivated, or matches sequences of cultivated bacteria and archaea in publicly accessible databases. Through developing a nomenclature system that represents the uncultivated majority, a path for communicating diversity will benefit particularly, those microbial scientists working in natural, bio-engineered, and host-associated ecosystems. 

Credit: Alison Murray/DRI.  

A proposed update to the International Code of Nomenclature of Prokaryotes would allow scientists to assign official names to uncultivated species of Bacteria and Archaea, such as the specimens shown in this enrichment culture of heat-loving Bacteria and Archaea from a hot spring. 

Credit: Anna-Louise Reysenbach.

“It sets the framework for a path forward to provide a structured way to communicate the vast untapped biodiversity of the microbial world within the scientific community and across the public domain” said Anna-Louise Reysenbach, Ph.D., Professor of Biology at Portland State University.  “That’s why this change is so important.”

The article and proposed plans are the culmination of a series of workshops that were funded by the National Science Foundation. The next step, says Murray, is to figure out an implementation strategy for moving forward with one of the two proposed plans, while engaging the many microbiologists who contributed to this consensus statement and others around the world who want to help see this change enacted. So far, many have been eager to participate.

“This is an exciting field to be in right now because we’re describing diversity of life on Earth and uncovering new phyla just like scientists were back in the 1800s when they were still discovering larger organisms,” Murray said. “Lots of paradigms have been changing in how we understand the way the world works, and how much diversity is out there – and this is another change that needs to be made. We’re going to need to change it or we’re going to live in chaos.”

“Lots of paradigms have been changing in how we understand the way the world works, and how much diversity is out there – and this is another change that needs to be made. We’re going to need to change it or we’re going to live in chaos.”

Additional information

This project was supported by the National Science Foundation. Additional authors included DRI’s Duane Moser, Ph.D.

To view the full text of the aricle “Roadmap for naming uncultivated Archaea and Bacteria”  in Nature Microbiology, please visit: https://www.nature.com/articles/s41564-020-0733-x

For more information on lead author Alison Murray, Ph.D. and her research, please visit: https://www.dri.edu/alison-murray-research/

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About the Desert Research Institute

The Desert Research Institute (DRI) is a recognized world leader in basic and applied interdisciplinary research. Committed to scientific excellence and integrity, DRI faculty, students, and staff have developed scientific knowledge and innovative technologies in research projects around the globe. Since 1959, DRI’s research has advanced scientific knowledge, supported Nevada’s diversifying economy, provided science-based educational opportunities, and informed policy makers, business leaders, and community members. With campuses in Reno and Las Vegas, DRI serves as the non-profit research arm of the Nevada System of Higher Education. For more information, please visit www.dri.edu.

 

Media Contact

Kelsey Fitzgerald
Science Writer, Desert Research Institute
775-741-0496
Kelsey.Fitzgerald@dri.edu
@DRIScience

Alison Murray selected to co-lead NASA’s Network for Ocean Worlds

Alison Murray selected to co-lead NASA’s Network for Ocean Worlds

New initiative will guide search for life in ice-covered water worlds beyond Earth

(Reno, Nevada – June 24, 2019) – Desert Research Institute microbial oceanographer and Antarctic researcher Alison Murray, Ph.D., has been selected to co-lead a new National Aeronautics and Space Administration (NASA) initiative to guide the search for life in ocean worlds beyond Earth.

The Network for Ocean Worlds (NOW) is the latest of four research coordination networks (RCNs) to be established by NASA, introduced today at AbSciCon 2019 in Seattle, Washington. NOW will foster research to identify ice-covered ocean worlds beyond Earth, characterize those oceans, investigate their habitability, search for life, and ultimately understand any life that is found.

“Ocean worlds beyond Earth have been a key research focus for NASA’s Planetary Science Division ever since the confirmation of ice-covered liquid water oceans on Jupiter’s moons,” explained Murray, who is best known for her work discovering the existence of microbial life at −13 °C within the ice-sealed Lake Vida in Antarctica in 2013.

Murray’s research has redefined the scientific view of biological diversity in Earth’s most extreme environments and provided critical insights into how microorganisms persist and function in extremely cold and harsh settings, including those that lack oxygen and biological sources of energy.

Murray will co-lead the network with Chris German at the Woods Hole Oceanographic Institution (WHOI) and Alyssa Rhoden at the Southwest Research Institute (SwRI).

“This new research coordination network will broaden our base of oceanographic expertise throughout the field of astrobiology by creating new collaborations and partnerships that will engage other federal agencies, international partners, philanthropic organizations and relevant NGOs,” added Murray. “This is an exciting time to both advance understanding of life in Earth’s polar ecosystems, and apply this understanding to cryospheres in ocean worlds of places like Europa, Enceladus and Titan.”

NOW will provide a forum for exchange of ideas and learning across the interdisciplinary spectrum of backgrounds and perspectives represented within the network of NASA-funded ocean worlds investigators.

“If we hope to find evidence of life beyond Earth, within the next human generation, then our best bet is to look toward the growing list of ice-covered ocean worlds right here in our own solar system,” said German. “And looking further ahead, if we want to understand the range of possible conditions that could support life anywhere beyond Earth, then we will simultaneously need to both continue exploring our own ocean for examples of extremes under which life can exist and continue developing exploration technologies that will be useful on/any/ocean world, including Earth.”

NOW’s first major focus will be to enhance the development of future NASA missions to Ocean Worlds, beginning with the Europa Clipper mission set to launch in June 2023.